OP0295 A 12-WEEK, RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED, PHASE 2B STUDY OF SAFETY, TOLERABILITY AND EFFICACY OF AR882 IN GOUT PATIENTS
Authors: J. C. C. Wei, R. M. Fleischmann, S. Morris, E. Polvent, Z. Shen, A. Clouser Roche, V. Hingorani, S. Yan, L. T. Yeh, R. Keenan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Despite gout being the most common inflammatory arthritis, there remains an unmet need for more effective treatment. AR882 is a novel, potent, and selective uric acid transporter 1 (URAT1) inhibitor in development for the treatment of gout and tophaceous gout. AR882 was well tolerated, including patients with various degrees of renal insufficiency, and has consistently demonstrated robust sUA lowering in multiple clinical trials. <h3>Objectives</h3> This global phase 2b trial is a randomized, double-blinded, placebo-controlled, 12-week study to evaluate the safety, tolerability, and efficacy of AR882 versus placebo in patients with gout. <h3>Methods</h3> The trial recruited patients 18 to 75 years of age with eGFR &gt;30 mL/min across 20 sites in the US, Australia, and Taiwan, who met the ACR/EULAR Gout Classification Criteria. Following gout flare prophylaxis for 10 days, patients received either once-daily AR882 50 mg, AR882 75 mg, or matching placebo for 12 weeks. Blood samples were collected every two weeks through Week 12 for laboratory tests, sUA and pharmacokinetic measurements. Efficacy endpoint was the percent of patients who reached sUA below 6, 5, 4, and 3 mg/dL. Safety including vital signs and electrocardiograms were collected throughout the study. <h3>Results</h3> A total of 140 patients were enrolled in this study. The majority of patients were male (93.6%) and white (58%), followed by Asian (28%) and Black or African (15%). The baseline sUA level was 8.6 (±1.3) mg/dL; mean age 54.3 (24-73) years; mean body weight 96.4 (±17.8) kg. Major comorbidities seen in patients included hypertension (47%), hyperlipidemia (35%), renal insufficiency (34%), arthritis (23%), diabetes (19%), cardiovascular disease (15%), lung disease (11%), and liver disease (5%). Following 12 weeks of treatment, median sUA levels were reduced from baseline 8.6 mg/dL to 3.5 mg/dL with 75 mg and 5.0 mg/dL with 50 mg. No change was observed in the placebo group. At Week 12, 89%, 82%, 63% and 29% of patients achieved &lt; 6, &lt;5, &lt;4 and &lt;3 mg/dL, respectively, in the 75 mg group. In the 50 mg group, 78%, 50%, 8% of patients achieved &lt; 6, &lt;5 and &lt;4 mg/dL, respectively. The sUA lowering effect was similar for three consecutive measurements between Week 8 and 12. There were no serious adverse events in AR882 treated patients. Mild or moderate adverse events including diarrhea, headache, and upper respiratory infection were observed in this study. A total of 65 gout flare incidents were observed and evenly distributed across groups during the 12-week treatment. <h3>Conclusion</h3> The majority of patients receiving AR882 had achieved sUA levels below 5 or 4 mg/dL, which are two key thresholds for more efficient flare and tophi reductions[1][2]. AR882 was well tolerated over the 12-week treatment period and patients with comorbidities did not require any adjustments in management of the diseases while treated with AR882. This study suggests AR882 may offer improved efficacy with acceptable safety compared to existing therapies for gout and may have utility in the treatment of patients across the spectrum of gout including those with severe or refractory disease. <h3>References</h3> [1]Perez-Ruiz F, Calabozo M, Pijoan JI, et al. Arthritis Rheum. 2002;47(4):356-60 [2]Richette P, Doherty M, Pascual E, et al. Ann Rheum Dis. 2017;76:29-42. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> James Cheng-Chung Wei: None declared, Roy M. Fleischmann Speakers bureau: AbbVie, Pfizer Inc, Consultant of: AbbVie, Amgen Inc., Biogen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos, Galvani, Gilead, GSK plc, Janssen Pharmaceuticals, Novartis AG, Union Chimique Belge (UCB), Grant/research support from: AbbVie, Amgen Inc., Biogen, Bristol Myers Squibb, Eli Lilly and Company, Flexion, Galapagos, Galvani, Genentech, Gilead, GSK plc, Horizon, Janssen Pharmaceuticals, Novartis AG, UCB, Viela, Sarah Morris Shareholder of: Arthrosi therapeutics, Employee of: Arthrosi therapeutics, Elizabeth Polvent Shareholder of: Arthrosi therapeutics, Employee of: Arthrosi therapeutics, Zancong Shen Shareholder of: Arthrosi therapeutics, Employee of: Arthrosi therapeutics, Andrea Clouser Roche Shareholder of: Arthrosi therapeutics, Employee of: Arthrosi therapeutics, Vijay Hingorani Consultant of: Arthrosi therapeutics, Shunqi Yan Shareholder of: Arthrosi therapeutics, Employee of: Arthrosi therapeutics, Li-Tain Yeh Shareholder of: Arthrosi therapeutics, Employee of: Arthrosi therapeutics, Robert Keenan Shareholder of: Arthrosi therapeutics, Employee of: Arthrosi therapeutics.